CARDIAC CHARACTERISTICS IN COPPER DEFICIENCY

缺铜时的心脏特征

• 批准号: 2691670
• 负责人: LYDIA MEDEIROS
• 金额: $ 6.56万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2691670
• 关键词: adenosinetriphosphatase; cell component structure /function; copper; cytochrome oxidase; disease /disorder etiology; gel mobility shift assay; gene expression; heart enlargement; laboratory rat; malnutrition; metal metabolism disorder; mitochondria; muscle hypertrophy; northern blottings; nutrition related tag; pathologic process; transcription factor; western blottings

DESCRIPTION: This revised application proposes to study the hypothesis that the impact of copper (Cu) deficiency on the heart acts as if it is due to a mitochondrial genetic disease which influences mitochondrial biogenesis, and that this effect is mediated by up-regulation of transcriptional factors which are responsible for the pathology and biochemistry. These changes include decreases in cytochrome c oxidase (CCO) activity and absolute amounts of the nuclear--encoded peptide subunits. In addition, the delta subunit of ATP synthase is markedly decreased and the e subunit of ATPase is significantly increased. These changes would induce the mitochondrial biogenesis and subsequent increase in cardiac mass that is observed in the hearts from copper-deficient rats. This proposal thus will examine three specific aims: 1. To determine if the expression and DNA binding activity of several transcriptional factors, know to regulate nuclear and mitochondrial encoded genes, are increased in hearts from copper deficient rats. 2. To determine if the gene regulatory program involved in mitochondrial biogenesis in copper deficiency is similar to the pressure-overload induced model of myocyte hypertrophy and 3. To determine if the functional properties of ATP synthase and inhibitory ATP synthase protein are decreased in hearts from copper-deficient rats.

描述：此修订后的申请旨在研究假设 铜 (Cu) 缺乏对心脏的影响就像 由于影响线粒体的线粒体遗传病 生物发生，并且这种效应是通过上调介导的 负责病理学的转录因子和 生物化学。这些变化包括细胞色素 c 氧化酶的减少 (CCO) 活性和核编码肽的绝对量 亚单位。此外，ATP合酶的δ亚基显着 减少，ATP酶的e亚基显着增加。这些 变化会诱导线粒体生物发生并随后增加 在缺铜大鼠的心脏中观察到的心脏质量。 因此，该提案将审查三个具体目标： 1. 确定是否 几种转录因子的表达和 DNA 结合活性 已知调节核和线粒体编码基因的因素是 缺铜大鼠心脏中的含量增加。 2. 判断是否 参与铜线粒体生物合成的基因调控程序 缺乏类似于压力超负荷诱导的肌细胞模型 3. 确定 ATP 的功能特性 心脏中合成酶和抑制性 ATP 合成酶蛋白减少 缺铜大鼠。